Unravelling the cause of stroke-induced cognitive decline
Authors: Michelle C Johansen
Journal: The Lancet Healthy Longevity (2023)

The realisation that we live in the era of a continuing aging population, combined with the controversy on the appropriateness of the administration of new therapeutics to slow the progression of Alzheimer's dementia,1de la Torre JC Gonzalez-Lima F The FDA approves aducanumab for Alzheimer's disease, raising important scientific questions1.J Alzheimers Dis. 2021; 82: 881-882Crossref Scopus (16) Google Scholar emphasises the importance of research that might lead us to a cure for dementia. For example, if there are other medical conditions that contribute to dementia that have known associated therapeutics, then perhaps one route by which to prevent dementia is to aggressively treat these other medical conditions. In The Lancet Healthy Longevity, Laura Sherlock and colleagues2Sherlock L Lee SF Katsanos AH et al.Cognitive performance following stroke, transient ischaemic attack, myocardial infarction, and hospitalisation: an individual participant data meta-analysis of six randomised controlled trials.Lancet Healthy Longev. 2023; 4: e665-e674Google Scholar in their meta-analysis of pooled data from six randomised clinical trials aimed to determine the individual effects (Z score differences) of cognitive performance between individuals with and without some of these medical conditions: stroke, transient ischaemic attack, myocardial infarction, and hospitalisation events. Leveraging a large sample size (N=64 106), and highlighting the limitations of previous work (ie, the absence of pre-morbid baseline cognitive measures and appropriate control for vascular risk factors), the authors estimated the years of cognitive aging associated with stroke and compared them with these other entities. The two tests that were used to determine cognitive performance are familiar to the reader, and used in clinical practice routinely: the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Although use of these tests increases generalisability, it is important to recognise that these tests do not diagnose dementia and are limited by practice and ceiling effects.3Davis DH Creavin ST Yip JL Noel-Storr AH Brayne C Cullum S Montreal Cognitive Assessment for the detection of dementia.Cochrane Database Syst Rev. 2021; 7CD010775 Google Scholar, 4Mitchell AJ A meta-analysis of the accuracy of the mini-mental state examination in the detection of dementia and mild cognitive impairment.J Psychiatr Res. 2009; 43: 411-431Crossref PubMed Scopus (743) Google Scholar The authors calculated the rate of cognitive Z score decline per year of age after the first event (mutually exclusive) of any stroke, transient ischaemic attack, myocardial infarction, or other event associated with hospitalisation. Of note, the authors decided to group participants with multiple diagnoses into the stroke category (stroke and transient ischaemic attack, or stroke and myocardial infarction) or the transient ischaemic attack category (transient ischaemic attack and myocardial infarction). This decision could bias results as some individuals in the stroke or transient ischaemic attack group actually have more disease burden (ie, more disease diagnoses, or poorer health), but this was a small percentage of the overall group. Risk factors for cognitive decline were appropriately treated as confounders in the analysis (eg, smoking and hypertension) and they also performed subgroup analyses by stroke subtype and severity. The statistical analyses appropriately accounted for trial differences and the effect of time. As described in the study, Sherlock and colleagues2Sherlock L Lee SF Katsanos AH et al.Cognitive performance following stroke, transient ischaemic attack, myocardial infarction, and hospitalisation: an individual participant data meta-analysis of six randomised controlled trials.Lancet Healthy Longev. 2023; 4: e665-e674Google Scholar found that about 2% of the population had a stroke during 3 years of follow-up, with the majority of them non-disabling and ischaemic. The authors found significantly poorer cognitive performance on both tests among individuals with stroke (equivalent to 18 years of aging), more severe stroke, and haemorrhagic stroke than those without stroke, or the other conditions. This finding confirms what has been found before,5Levine DA Galecki AT Langa KM et al.Trajectory of cognitive decline after incident stroke.JAMA. 2015; 314: 41-51Crossref PubMed Scopus (296) Google Scholar, 6Levine DA Wadley VG Langa KM et al.Risk factors for poststroke cognitive decline: the REGARDS Study (reasons for geographic and racial differences in stroke).Stroke. 2018; 49: 987-994Crossref PubMed Scopus (74) Google Scholar, 7Koton S Pike JR Johansen M et al.Association of ischemic stroke incidence, severity, and recurrence with dementia in the atherosclerosis risk in communities cohort study.JAMA Neurol. 2022; 79: 271-280Crossref PubMed Scopus (33) Google Scholar but is a more severe decline than some have reported, emphasising the importance of a stroke event in the cognitive trajectory of these patients. Surprisingly, the authors did not find a difference, by age or sex, in the rate of cognitive decline and also did not find a significant decline in scores among individuals with myocardial infarction, or other hospitalisation event. Other work has shown the importance of an acute myocardial infarction on cognition and increased prevalence of dementia among those living with myocardial infarction.8Johansen MC Langton-Frost N Gottesman RF The role of cardiovascular disease in cognitive impairment.Curr Geri Rep. 2020; 9: 1-9Crossref Scopus (12) Google Scholar, 9Johansen MC Ye W Gross A et al.Association between acute myocardial infarction and cognition.JAMA Neurol. 2023; 80: 723-731Crossref Scopus (5) Google Scholar, 10Prajna TD Ischemic heart disease and risk of development of cognitive disorders: a literature review.Eur J Mol Clin Med. 2022; 9: 2096-2116Google Scholar Perhaps participants in a randomised trial represent a healthier population, with fewer vascular comorbidities, as the authors themselves acknowledge, or the amount of follow-up (average of 4 years) was not sufficient to capture the decline reported by others. Another limitation acknowledged by the authors is that the population as a whole was well-educated with high baseline cognitive scores on average. They found the most severe decline among individuals with the worst baseline scores, so it could be that the magnitude of decline might be even higher in a population in which the baseline education level was lower. Although there are some limitations, the large sample size, use of standardised randomised data, careful accounting for cohort effects, vascular risk factors, and follow-up time emphasises what the clinician has long recognised; stroke has a deleterious effect on cognition, and the more severe the initial event, the more severe the decline. Again, it is impossible to diagnose dementia based on two tests scores, but one could argue that any decline in cognition is a meaningful decline if you are the patient. The authors appropriately highlight the importance of acute stroke therapies as an important take-home message as prevention of ischaemia and reduction of infarct volume not only helps physical recovery, but prevents a cognitive hit as well. Although we wait for a dementia cure, preventing decline by addressing important disease states such as stroke, is an important first step. I declare no competing interests. Cognitive performance following stroke, transient ischaemic attack, myocardial infarction, and hospitalisation: an individual participant data meta-analysis of six randomised controlled trialsStroke has a substantial effect on cognition. The effects of transient ischaemic attack were small, whereas myocardial infarction and hospitalisation had a neutral effect. Prevention of stroke could lead to a reduction in cognitive ageing in those at greatest risk. Full-Text PDF Open Access